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Plastin 3 promotes motor neuron axonal growth and extends survival in a mouse model of spinal muscular atrophy


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Alrafiah, A, Karyka, E, Coldicott, I, Iremonger, K, Lewis, KE ORCID: 0000-0003-1264-464X, Ning, K and Azzouz, M 2018 , 'Plastin 3 promotes motor neuron axonal growth and extends survival in a mouse model of spinal muscular atrophy' , Molecular Therapy - Methods & Clinical Development, vol. 9 , pp. 81-89 , doi: 10.1016/j.omtm.2018.01.007.

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Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease. SMA is caused by mutations in the survival motor neuron gene (SMN1), leading to reduced levels of SMN protein in the CNS. The actin-binding protein plastin 3 (PLS3) has been reported as a modifier for SMA, making it a potential therapeutic target. Here, we show reduced levels of PLS3 protein in the brain and spinal cord of a mouse model of SMA. Our study also revealed that lentiviral-mediated PLS3 expression restored axonal length in cultured Smn-deficient motor neurons. Delivery of adeno-associated virus serotype 9 (AAV9) harboring Pls3 cDNA via cisterna magna in SMNΔ7 mice, a widely used animal model of SMA, led to high neuronal transduction efficiency. PLS3 treatment allowed a small but significant increase of lifespan by 42%. Although there was no improvement of phenotype, this study has demonstrated the potential use of Pls3 as a target for gene therapy, possibly in combination with other disease modifiers.

Item Type: Article
Authors/Creators:Alrafiah, A and Karyka, E and Coldicott, I and Iremonger, K and Lewis, KE and Ning, K and Azzouz, M
Keywords: spinal muscular atrophy, plastin 3, gene therapy
Journal or Publication Title: Molecular Therapy - Methods & Clinical Development
Publisher: Elsevier BV
ISSN: 2329-0501
DOI / ID Number: 10.1016/j.omtm.2018.01.007
Copyright Information:

Copyright 2018 The Author(s). Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

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